Breast cancer is the most common malignancy among women and has one of the highest fatality rates of all cancers affecting females. Breast cancer remains the leading cause of cancer deaths in women aged 20-59.
It is well established that prolactin and growth hormone play a role in the development and progression of breast cancer. For example, higher serum level of lactogenic hormones have been found in some breast cancer patients, and 40-70% of breast cancer biopsies were positive for the presence of the prolactin receptor. Indeed, most human breast cancer cells in culture contain prolactin receptors, and the majority of breast cancer cell lines overexpress the prolactin receptor 2-10 fold. For example, T47D and MCF-7 both contain high levels of prolactin receptor and are often used as a model demonstrating the relationship between lactogenic hormones and breast cancer. Accordingly, numerous approaches to breast cancer therapy are directed to prolactin antagonists, and methods of blocking the prolactin receptor.
Similarly, a high serum level of growth hormone was found to induce the formation of breast cancer, while reduction of the circulating level of growth hormone correlated with the regression of breast cancer.
The cancer stem cell (CSC) theory states that tumors are organized in a cellular hierarchy, in which CSCs are the only cells with unlimited proliferation potential and the capability of driving tumor growth and progression. Therefore, efforts are also being made to develop cancer therapeutics which target cancer stem cells. However, recent studies show that the use of conventional chemotherapy in neoadjuvant regimens could actually lead to enrichment in CSCs, suggesting that CSCs may be generally resistant to chemotherapy. Indeed, the lack of responsiveness of CSCs to chemotherapy explains why clinically, tumor size is often initially reduced in response to chemotherapeutic drugs but then relapses.
Several lines of evidence have strongly linked PRL to breast cancer development, and expression levels of prolactin receptors (PRLR) reportedly are higher in human breast cancer cells than in normal breast epithelial cells (Reynolds et al., Endocrinology, 138:5555-60 (1997)) or in surgically removed breast cancer tissues (Touraine, Martini P. et al., Increased Expression Of Prolactin Receptor Gene In Human Breast Tumors Versus Contiguous Normal Breast Tissues, (Abstract) 79th Annual Meeting of Endocrine Society, p. 113, (1997)). Prolactin has also been shown to act as an anti-apoptotic agent and anti-prolactin agents have been shown to induce apoptosis in breast cancer cells (Chen et al., Clin. Cancer Res. 5:3583-93 (1999)). The present invention, however, discloses the unexpected discovery that prolactin can be used in a method for treating breast cancer.